3C4M

Structure of human parathyroid hormone in complex with the extracellular domain of its G-protein-coupled receptor (PTH1R)

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Protein Modification Annotation

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
C	d3c4mc1	Peptides	Parathyroid hormone fragments (residues between 1 and 39)	Parathyroid hormone fragments (residues between 1 and 39)	Parathyroid hormone fragments (residues between 1 and 39)	Parathyroid hormone fragments (residues between 1 and 39)	(Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d3c4md1	Peptides	Parathyroid hormone fragments (residues between 1 and 39)	Parathyroid hormone fragments (residues between 1 and 39)	Parathyroid hormone fragments (residues between 1 and 39)	Parathyroid hormone fragments (residues between 1 and 39)	(Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
B	SCOP2B Superfamily	Type 2 solute binding protein-like	8058187	3000083	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Type 2 solute binding protein-like	8058187	3000083	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
B	HRM	e3c4mB4	A: few secondary structure elements	X: Hormone receptor domain (HRM, Pfam 02793) (From Topology)	H: Hormone receptor domain (HRM, Pfam 02793) (From Topology)	T: Hormone receptor domain (HRM, Pfam 02793)	F: HRM	ECOD (1.6)
A	SBP_bac_1_C,SBP_bac_1_N_2	e3c4mA2	A: a/b three-layered sandwiches	X: Periplasmic binding protein-like II (From Topology)	H: Periplasmic binding protein-like II (From Topology)	T: Periplasmic binding protein-like II	F: SBP_bac_1_C,SBP_bac_1_N_2	ECOD (1.6)
A	HRM	e3c4mA1	A: few secondary structure elements	X: Hormone receptor domain (HRM, Pfam 02793) (From Topology)	H: Hormone receptor domain (HRM, Pfam 02793) (From Topology)	T: Hormone receptor domain (HRM, Pfam 02793)	F: HRM	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	3.40.190.10	Alpha Beta	3-Layer(aba) Sandwich	D-Maltodextrin-Binding Protein	domain 2	CATH (4.3.0)
B	4.10.1240.10	Few Secondary Structures	Irregular	Hormone receptor fold	GPCR, family 2, extracellular hormone receptor domain	CATH (4.3.0)
A	3.40.190.10	Alpha Beta	3-Layer(aba) Sandwich	D-Maltodextrin-Binding Protein	domain 2	CATH (4.3.0)
A	4.10.1240.10	Few Secondary Structures	Irregular	Hormone receptor fold	GPCR, family 2, extracellular hormone receptor domain	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF02793	Hormone receptor domain (HRM)	Hormone receptor domain	-	Family
C, D	PF01279	Parathyroid hormone family (Parathyroid)	Parathyroid hormone family	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	Fusion protein of Maltose-binding periplasmic protein and Parathyroid hormone/parathyroid hormone-related peptide receptor	transporter activity carbohydrate transmembrane transporter activity transmembrane transporter activity oligosaccharide binding binding disaccharide binding carbohydrate binding maltose binding identical protein binding protein binding protein homodimerization activity protein dimerization activity amide binding peptide hormone binding transporter activity carbohydrate transmembrane transporter activity transmembrane transporter activity oligosaccharide binding binding disaccharide binding carbohydrate binding maltose binding identical protein binding protein binding protein homodimerization activity protein dimerization activity amide binding peptide hormone binding hormone binding peptide receptor activity molecular transducer activity G protein-coupled receptor activity G protein-coupled peptide receptor activity transmembrane signaling receptor activity signaling receptor activity parathyroid hormone receptor activity	cellular response to stimulus cellular response to stress response to stimulus DNA damage response response to stress cellular process cell chemotaxis chemotaxis response to external stimulus cellular response to chemical stimulus taxis response to chemical cell migration cell motility cellular response to stimulus cellular response to stress response to stimulus DNA damage response response to stress cellular process cell chemotaxis chemotaxis response to external stimulus cellular response to chemical stimulus taxis response to chemical cell migration cell motility locomotion localization transport organic substance transport carbohydrate transport oligosaccharide transport disaccharide transport establishment of localization maltose transport polysaccharide localization dextrin transport macromolecule localization maltodextrin transmembrane transport polysaccharide transport response to organic substance response to disaccharide response to oxygen-containing compound detection of maltose stimulus detection of stimulus response to carbohydrate detection of chemical stimulus detection of disaccharide stimulus response to maltose detection of carbohydrate stimulus developmental process multicellular organismal process ossification bone mineralization animal organ development anatomical structure development biomineral tissue development tissue development multicellular organism development skeletal system development system development cell population proliferation regulation of biological process regulation of cellular process signaling biological regulation cell communication adenylate cyclase-modulating G protein-coupled receptor signaling pathway G protein-coupled receptor signaling pathway signal transduction inorganic ion homeostasis intracellular calcium ion homeostasis homeostatic process calcium ion homeostasis cellular homeostasis chemical homeostasis intracellular monoatomic cation homeostasis monoatomic ion homeostasis intracellular chemical homeostasis monoatomic cation homeostasis intracellular monoatomic ion homeostasis osteoblast development cellular developmental process cell differentiation cell development osteoblast differentiation embryo development ending in birth or egg hatching chordate embryonic development embryo development in utero embryonic development anatomical structure maturation cell maturation developmental maturation adenylate cyclase-activating G protein-coupled receptor signaling pathway positive regulation of cell population proliferation regulation of cell population proliferation positive regulation of biological process positive regulation of cellular process cell surface receptor signaling pathway negative regulation of cell population proliferation negative regulation of cellular process negative regulation of biological process phospholipase C-activating G protein-coupled receptor signaling pathway connective tissue development chondrocyte differentiation cartilage development regulation of inositol phosphate biosynthetic process positive regulation of phosphate metabolic process regulation of primary metabolic process positive regulation of metabolic process regulation of small molecule metabolic process regulation of phosphate metabolic process phosphate-containing compound metabolic process polyol biosynthetic process organic substance biosynthetic process small molecule metabolic process phosphorus metabolic process polyol metabolic process positive regulation of phosphorus metabolic process regulation of alcohol biosynthetic process cellular metabolic process carbohydrate biosynthetic process regulation of cellular metabolic process primary metabolic process positive regulation of inositol phosphate biosynthetic process biosynthetic process organophosphate biosynthetic process inositol phosphate biosynthetic process regulation of phosphorus metabolic process metabolic process positive regulation of carbohydrate metabolic process regulation of metabolic process cellular biosynthetic process organic hydroxy compound metabolic process positive regulation of cellular metabolic process alcohol metabolic process inositol phosphate metabolic process organic substance metabolic process positive regulation of biosynthetic process regulation of carbohydrate metabolic process regulation of biosynthetic process carbohydrate metabolic process small molecule biosynthetic process regulation of cellular biosynthetic process organophosphate metabolic process organic hydroxy compound biosynthetic process alcohol biosynthetic process regulation of carbohydrate biosynthetic process positive regulation of small molecule metabolic process positive regulation of alcohol biosynthetic process positive regulation of cellular biosynthetic process multicellular organismal-level homeostasis tissue remodeling bone remodeling anatomical structure homeostasis tissue homeostasis bone resorption G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	ATPase dependent transmembrane transport complex protein-containing complex plasma membrane protein complex membrane plasma membrane membrane protein complex cellular anatomical entity transporter complex ATP-binding cassette (ABC) transporter complex cell periphery transmembrane transporter complex ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing maltose transport complex periplasmic space ATPase dependent transmembrane transport complex protein-containing complex plasma membrane protein complex membrane plasma membrane membrane protein complex cellular anatomical entity transporter complex ATP-binding cassette (ABC) transporter complex cell periphery transmembrane transporter complex ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing maltose transport complex periplasmic space outer membrane-bounded periplasmic space cell envelope apical part of cell plasma membrane region apical plasma membrane basal part of cell basal plasma membrane basolateral plasma membrane intracellular anatomical structure cytoplasm receptor complex membrane-bounded organelle intracellular organelle organelle nucleus intracellular membrane-bounded organelle
C, D	Parathyroid hormone	parathyroid hormone receptor binding protein binding binding signaling receptor binding G protein-coupled receptor binding type 1 parathyroid hormone receptor binding molecular function activator activity molecular function regulator activity signaling receptor regulator activity receptor ligand activity signaling receptor activator activity peptide hormone receptor binding hormone receptor binding hormone activity	response to stimulus response to chemical response to xenobiotic stimulus response to organic substance response to parathyroid hormone response to hormone response to endogenous stimulus magnesium ion homeostasis inorganic ion homeostasis chemical homeostasis homeostatic process monoatomic ion homeostasis monoatomic cation homeostasis developmental process response to stimulus response to chemical response to xenobiotic stimulus response to organic substance response to parathyroid hormone response to hormone response to endogenous stimulus magnesium ion homeostasis inorganic ion homeostasis chemical homeostasis homeostatic process monoatomic ion homeostasis monoatomic cation homeostasis developmental process multicellular organismal process ossification bone mineralization animal organ development anatomical structure development biomineral tissue development tissue development multicellular organismal-level homeostasis homeostasis of number of cells within a tissue anatomical structure homeostasis tissue homeostasis homeostasis of number of cells organic substance metabolic process biosynthetic process cellular biosynthetic process cellular metabolic process organic substance biosynthetic process metabolic process cellular process macromolecule metabolic process macromolecule biosynthetic process multicellular organism development skeletal system development system development regulation of cellular process positive regulation of biological process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process positive regulation of macromolecule metabolic process positive regulation of cellular process regulation of biosynthetic process regulation of biological process biological regulation regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression regulation of cellular biosynthetic process regulation of gene expression positive regulation of gene expression regulation of macromolecule biosynthetic process regulation of metabolic process positive regulation of cellular biosynthetic process RNA metabolic process primary metabolic process nucleobase-containing compound biosynthetic process nucleic acid metabolic process RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription organic cyclic compound metabolic process nucleic acid biosynthetic process transcription by RNA polymerase II organic cyclic compound biosynthetic process negative regulation of apoptotic process in bone marrow cell negative regulation of programmed cell death apoptotic process in bone marrow cell regulation of apoptotic process in bone marrow cell regulation of apoptotic process negative regulation of biological process regulation of programmed cell death cell death negative regulation of apoptotic process negative regulation of cellular process apoptotic process programmed cell death regulation of generation of precursor metabolites and energy regulation of primary metabolic process positive regulation of glycogen metabolic process regulation of small molecule metabolic process small molecule metabolic process carbohydrate biosynthetic process hexose metabolic process positive regulation of glucose metabolic process positive regulation of glycogen biosynthetic process energy reserve metabolic process positive regulation of carbohydrate metabolic process regulation of glycogen metabolic process monosaccharide metabolic process regulation of glycogen biosynthetic process glucan biosynthetic process energy derivation by oxidation of organic compounds regulation of glucan biosynthetic process regulation of polysaccharide metabolic process polysaccharide metabolic process glucan metabolic process regulation of carbohydrate metabolic process regulation of glucose metabolic process carbohydrate metabolic process polysaccharide biosynthetic process glycogen metabolic process generation of precursor metabolites and energy glycogen biosynthetic process regulation of polysaccharide biosynthetic process regulation of carbohydrate biosynthetic process positive regulation of small molecule metabolic process glucose metabolic process phosphate ion homeostasis signaling cell-cell signaling cell communication intracellular calcium ion homeostasis calcium ion homeostasis cellular homeostasis intracellular monoatomic cation homeostasis intracellular chemical homeostasis intracellular monoatomic ion homeostasis regulation of developmental process regulation of biomineral tissue development regulation of bone mineralization positive regulation of ossification positive regulation of developmental process positive regulation of biomineral tissue development regulation of multicellular organismal process regulation of multicellular organismal development positive regulation of bone mineralization positive regulation of multicellular organismal process regulation of ossification response to alcohol response to oxygen-containing compound response to ethanol cellular response to stimulus adenylate cyclase-activating G protein-coupled receptor signaling pathway adenylate cyclase-modulating G protein-coupled receptor signaling pathway G protein-coupled receptor signaling pathway signal transduction response to metal ion response to lead ion response to inorganic substance cell population proliferation positive regulation of cell population proliferation positive regulation of cell proliferation in bone marrow cell proliferation in bone marrow regulation of cell proliferation in bone marrow regulation of cell population proliferation response to nutrient levels response to vitamin D response to lipid response to nutrient response to vitamin response to organic cyclic compound regulation of phospholipase activity positive regulation of phospholipase activity regulation of catalytic activity positive regulation of catalytic activity positive regulation of phospholipase C activity positive regulation of lipase activity regulation of molecular function positive regulation of molecular function positive regulation of hydrolase activity regulation of phospholipase C activity regulation of hydrolase activity regulation of lipase activity activation of phospholipase C activity hormone-mediated signaling pathway cellular response to endogenous stimulus cellular response to organic substance cellular response to hormone stimulus apoptotic signaling pathway cellular response to chemical stimulus hormone-mediated apoptotic signaling pathway ribose phosphate metabolic process carbohydrate derivative metabolic process cyclic nucleotide metabolic process purine nucleotide metabolic process ribonucleotide metabolic process nucleobase-containing small molecule metabolic process phosphate-containing compound metabolic process phosphorus metabolic process nucleoside phosphate metabolic process organonitrogen compound metabolic process cAMP metabolic process cyclic purine nucleotide metabolic process nucleotide metabolic process purine-containing compound metabolic process organophosphate metabolic process purine ribonucleotide metabolic process regulation of cartilage development regulation of chondrocyte differentiation connective tissue development cellular developmental process negative regulation of cartilage development negative regulation of chondrocyte differentiation regulation of cell differentiation cell differentiation negative regulation of cell differentiation negative regulation of developmental process chondrocyte differentiation negative regulation of multicellular organismal process cartilage development negative regulation of cellular metabolic process negative regulation of macromolecule metabolic process negative regulation of metabolic process negative regulation of cellular biosynthetic process negative regulation of gene expression negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process positive regulation of cell communication regulation of signaling positive regulation of signal transduction regulation of signal transduction positive regulation of response to stimulus regulation of response to stimulus regulation of cell communication positive regulation of signaling response to cadmium ion small GTPase-mediated signal transduction Rho protein signal transduction intracellular signal transduction intracellular signaling cassette regulation of leukocyte proliferation osteoclast proliferation regulation of osteoclast proliferation positive regulation of osteoclast proliferation leukocyte proliferation positive regulation of leukocyte proliferation bone maturation regulation of bone mineralization involved in bone maturation negative regulation of biomineral tissue development negative regulation of bone mineralization ossification involved in bone maturation bone development bone mineralization involved in bone maturation developmental maturation negative regulation of bone mineralization involved in bone maturation negative regulation of ossification anatomical structure maturation animal organ maturation regulation of RNA metabolic process regulation of nucleobase-containing compound metabolic process regulation of transcription by RNA polymerase II positive regulation of nucleobase-containing compound metabolic process positive regulation of transcription by RNA polymerase II positive regulation of RNA metabolic process regulation of DNA-templated transcription positive regulation of DNA-templated transcription regulation of RNA biosynthetic process positive regulation of RNA biosynthetic process regulation of localization hexose transmembrane transport glucose import transport carbohydrate transport localization positive regulation of transmembrane transport glucose transmembrane transport regulation of glucose import positive regulation of glucose transmembrane transport regulation of transport organic substance transport establishment of localization transmembrane transport regulation of glucose transmembrane transport regulation of transmembrane transport positive regulation of transport monosaccharide transmembrane transport positive regulation of glucose import carbohydrate transmembrane transport regulation of inositol phosphate biosynthetic process positive regulation of phosphate metabolic process regulation of phosphate metabolic process polyol biosynthetic process polyol metabolic process positive regulation of phosphorus metabolic process regulation of alcohol biosynthetic process positive regulation of inositol phosphate biosynthetic process organophosphate biosynthetic process inositol phosphate biosynthetic process regulation of phosphorus metabolic process organic hydroxy compound metabolic process alcohol metabolic process inositol phosphate metabolic process small molecule biosynthetic process organic hydroxy compound biosynthetic process alcohol biosynthetic process positive regulation of alcohol biosynthetic process tissue remodeling bone remodeling bone resorption response to fibroblast growth factor response to growth factor	extracellular region cellular anatomical entity extracellular space

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR006061	Solute-binding family 1, conserved site	Conserved Site
A, B	IPR006060	Maltose/Cyclodextrin ABC transporter, substrate-binding protein	Family
A, B	IPR006059	Bacterial-type extracellular solute-binding protein	Family
A, B	IPR017983	GPCR, family 2, secretin-like, conserved site	Conserved Site
A, B	IPR036445	GPCR family 2, extracellular hormone receptor domain superfamily	Homologous Superfamily
A, B	IPR002170	GPCR, family 2, parathyroid hormone receptor	Family
A, B	IPR000832	GPCR, family 2, secretin-like	Family
A, B	IPR017981	GPCR, family 2-like, 7TM	Domain
A, B	IPR001879	GPCR, family 2, extracellular hormone receptor domain	Domain
C, D	IPR001415	Parathyroid hormone/parathyroid hormone-related protein	Family
C, D	IPR003625	Parathyroid hormone	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: Q03431	Eiken syndrome metaphyseal chondrodysplasia, Jansen type rickets chondrodysplasia Blomstrand type Ollier disease primary failure of tooth eruption hyperparathyroidism medulloblastoma osteogenesis imperfecta psoriasis adrenal cortex adenoma breast carcinoma Glucocorticoid Induced Osteoporosis large cell medulloblastoma malignant glioma Eiken syndrome metaphyseal chondrodysplasia, Jansen type rickets chondrodysplasia Blomstrand type Ollier disease primary failure of tooth eruption hyperparathyroidism medulloblastoma osteogenesis imperfecta psoriasis adrenal cortex adenoma breast carcinoma Glucocorticoid Induced Osteoporosis large cell medulloblastoma malignant glioma postmenopausal osteoporosis adrenal cortex carcinoma hepatocellular carcinoma hypoparathyroidism lung disease malignant mesothelioma tooth ankylosis glioblastoma intellectual disability
C, D	Pharos: P01270	rickets hypercalcemia disease hyperphosphatemia uremia Hypocalcemia hypertensive disorder anemia osteoporosis secondary hyperparathyroidism hyperostosis hypoparathyroidism, familial isolated 1 nevoid basal cell carcinoma syndrome familial hypoparathyroidism congestive heart failure postmenopausal osteoporosis rickets hypercalcemia disease hyperphosphatemia uremia Hypocalcemia hypertensive disorder anemia osteoporosis secondary hyperparathyroidism hyperostosis hypoparathyroidism, familial isolated 1 nevoid basal cell carcinoma syndrome familial hypoparathyroidism congestive heart failure postmenopausal osteoporosis adenoma kidney failure bone fracture multiple endocrine neoplasia calcinosis nephrolithiasis osteomalacia diabetes mellitus primary hyperparathyroidism hypoparathyroidism cancer digestive system disease pseudohypoparathyroidism hyperparathyroidism hyperthyroidism hypophosphatemia bone resorption disease nephrocalcinosis osteitis fibrosa renal osteodystrophy heart failure

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
C, D	NH2	RESID: AA0081 , AA0083 , AA0084 , AA0086 , AA0087 , AA0088 , AA0090 , AA0091 , AA0092 , AA0093 , AA0095 , AA0096 , AA0097 , AA0098 , AA0099 , AA0100 PSI-MOD : L-alanine amide MOD:00090 , L-asparagine amide MOD:00092 , L-aspartic acid 1-amide MOD:00093 , L-glutamine amide MOD:00095 , L-glutamic acid 1-amide MOD:00096 , glycine amide MOD:00097 , L-isoleucine amide MOD:00099 , L-leucine amide MOD:00100 , L-lysine amide MOD:00101 , L-methionine amide MOD:00102 , L-proline amide MOD:00104 , L-serine amide MOD:00105 , L-threonine amide MOD:00106 , L-tryptophan amide MOD:00107 , L-tyrosine amide MOD:00108 , L-valine amide MOD:00109

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.